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Protocol Details

Intrathecal 2-Hydroxypropyl-Beta-Cyclodextrin for Neurological Decline in Patients with Niemann-Pick Disease Type C1

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Child Health and Human Development (NICHD)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)



Expanded Access

Recruitment Keyword(s)



Niemann-Pick Disease, Type C

Investigational Drug(s)


Investigational Device(s)



Drug: VTS-270

Supporting Site

National Institute of Child Health and Human Development

Niemann-Pick Type C1 (NPC1) disease is a rare, fatal, autosomal recessive, neurodegenerative lysosomal lipid storage disorder caused by a mutation of the NPC1 gene. The disease is characterized by the inability to properly metabolize cholesterol and other lipids within the cell, causing cholesterol to accumulate in the brain, liver and spleen. Although symptoms can appear well into adulthood, the typical onset of symptoms is in early childhood, and with earlier onset, there is more rapid progression of disease and death often before age 20. Owing to different clinical presentations and course of disease, NPC1 disease is typically categorized as early-infantile onset (< 2 years), late-infantile onset (2 to < 6 years), juvenile onset (6 to < 15 years) and adolescent/adult onset (> 15 years). Neurologic symptoms of disease include cerebellar ataxia, dysarthria, seizures, vertical gaze palsy, motor impairment, dysphagia, psychotic episodes, and progressive dementia. Hepatosplenomegaly occurs in 85% of cases and is more frequent in those with disease onset in infancy, but this frequency may decrease over time. The initial focus of this drug development program will be on those with juvenile onset (6 to 21 years of age) owing to the shorter lifespan in those subjects with infantile onset forms of NPC1 disease, (death within 5 years for early infantile onset and between ages 7 and 12 for late-infantile onset) and the relatively slow disease progression in those with adult onset. At present, miglustat (Zavesca), an imino sugar, has been approved for the treatment of subjects with NPC1 disease in approximately 70 countries. Miglustat is not approved in the US for the treatment of NPC1 due to its modest effects on an endpoint which was not clearly clinically relevant as a measure of therapeutic response. To help a dress this significant unmet medical need, research has identified the cholesterol sequestration agent, 2-hydroxypropyl-beta -cyclodextrin (HP-beta-CD), as a potential treatment for subjects with NPC1 disease. The development of HP- beta -CD for NPC1 is supported by data generated in preclinical models of NPC1 disease in mouse and cat where HP-beta-CD has been found to: - Mobilize excess cellular cholesterol caused by the metabolic deficiency as demonstrated in in vitro and in vivo models - Delay onset of signs and symptoms by approximately 100% and prolong survival by approximately 2 fold in the mouse NPC1 model - Prolong survival by approximately 8 fold, decrease Purkinje cell loss and improve gait in the cat NPC1 model. On the basis of these findings, an ongoing Investigator Sponsored Investigational New Drug Application (iIND) is assessing the safety and preliminary efficacy of IT HP-beta-CD administered every 2 or 4 weeks.

We are requesting to be added to forementioned iIND /expanded access protocol (EAP), to treat one patient. Subject ID 1108-006 (16CH0016), a 20 year old male from Mexico, was enrolled on protocol 16-CH-0016 (VTS301) in January 2017 and randomized to the treatment arm for lumbar intrathecal administration of adrabetadex (VTS-270) every two weeks. During the randomized period of the trial his neurologic symptoms of NPC1 disease remained stable with some mild perceived improvement in fine and gross motor areas by his family and study team members. In January 2018 he experienced an acute episode of dystonic storm, which has been reported in NPC1 patients and has an unknown association to the study drug. Study drug dosing was held during a prolonged inpatient admission to the NIH CRC, during which his dystonic movements were stabilized with pharmacologic management and study drug dosing resumed in April 2018. Since then, his neurologic manifestations of NPC have remained stable (per report from family members, observations by the NIH medical team and supported by NPC clinical severity scores). Continuation of dosing at the NIH is necessary for NPC stabilization of his known dystonia; there is no local medical care in Mexico to appropriately manage care. Dosing frequency was changed from every 2 weeks to monthly dosing in March 2020 due to Covid-19, to minimize the amount of travel necessary for the patient and his mother and thus reduce their risk of exposure. The monthly dosing is supported by data from the Phase 1 IT study and is allowed in both protocol 16-CH-0016 as well as the Rush expanded access protocol on which we are submitting to continue dosing.

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1) Age 4 and under (up to 5th birthday)

2) Weight of 7 kg or higher

3) Documentation that the patient does not qualify for any currently enrolling interventional clinical trial for NPC in the USA

4) Diagnosis of NPC confirmed based on documentation of molecular pathogenic variants in an NPC gene as follows: Patients with 2 pathogenic mutations in NPC1 or NPC2 (pathogenic defined as a previously known mutation seen in other NPC patients, or one not previously seen but determined to be pathogenic based on standard ACMG guidelines).

5) Any one of the following 4 symptoms, indicating rapid disease progression:

a. Vertical supranuclear gaze palsy (VSGP) observed on exam by two independent qualified physicians

b. Delayed gross motor milestone (not walking by two years) or demonstration of regression (could walk but now requires assistive device for ambulation)

c. Dysphagia on a video swallowing study

d. Seizures on EEG

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Forbes D. Porter, M.D.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CRC BG RM 5-2571
(301) 435-4432

Derek Alexander
National Institute of Child Health and Human Development (NICHD)
BG 10-CRC RM 1-3330
(301) 827-0387

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

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